Ring closing metathesis of prochiral oxaenediynes to racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans

Abstract

Prochiral 4-(allyloxy)hepta-1,6-diynes, optionally modified in the positions 1 and 7 with an alkyl or ester group, undergo chemoselective ring closing enyne metathesis yielding racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans. Among the catalysts tested, Grubbs 1st generation precatalyst in the presence of ethene (Mori conditions) gave superior results compared to more stable Grubbs or Hoveyda-Grubbs 2nd generation precatalysts. This is probably caused by suppression of subsequent side-reactions of the enyne metathesis product with ethene. On the other hand, 2nd generation precatalysts gave better yields in the absence of ethene. The metathesis products, containing both triple bond and conjugated system, can be successfully orthogonally modified. For example, metathesis product of 5-(allyloxy)nona-2,7-diyne reacted chemo- and stereoselectively by Diels-Alder reaction with N-phenylmaleimide affording tricyclic products as the mixture of two separable diastereoisomers, the configuration of which was estimated by DFT computations. The reported enediyne metathesis paves the way to enantioselective enyne metathesis yielding chiral building blocks for compounds with potential biological activity, e.g. norsalvinorin or cacospongionolide B.